Tissue-Based Biomarkers for the Risk Stratification of Men With Clinically Localized Prostate Cancer

Basourakos, Spyridon P.; Tzeng, Michael; Lewicki, Patrick; Patel, Krishnan R.; Venkat, Siv; Shoag, Jonathan; Gorin, Michael A.; Barbieri, Christopher E.; Hu, Jim C.

doi:10.3389/fonc.2021.676716

Cited by 25 publications

(14 citation statements)

References 78 publications

(89 reference statements)

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“…The use of molecular markers in risk stratification for PC is an active area of research with significant future potential. New tissue-based genomic tests, such as the Decipher, Prolaris, PTEN/TMPRSS2:ERG, Oncotype DX, ConfirmMDx, and ProMark, are being investigated to improve the detection and risk assessment of PC . Future research will focus on validating these biomarkers and determining their effectiveness in guiding treatment decisions.…”

Section: Discussionmentioning

confidence: 99%

Risk of Short-Term Prostate-Specific Antigen Recurrence and Failure in Patients With Prostate Cancer

Sayan,

Huang,

Xie

et al. 2023

JAMA Netw Open

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ImportanceA shorter time interval to prostate-specific antigen (PSA) failure is associated with worse clinical outcomes; however, specific factors defining this state remain unknown.ObjectiveTo evaluate the factors of a short time interval to PSA failure in order to identify patients for treatment escalation randomized clinical trials.Design, Setting, and ParticipantsThis secondary analysis of a randomized clinical trial was a secondary analysis of the Dana-Farber Cancer Institute 05-043 trial and included 350 patients with nonmetastatic unfavorable risk prostate cancer (PC).InterventionsPatients were randomized 1:1 to receive androgen deprivation therapy (ADT) and radiation therapy (RT) plus docetaxel vs ADT and RT.Main Outcomes and MeasuresCumulative incidence rates curves of PSA failure, defined as PSA nadir plus 2 ng/mL or initiation of salvage therapies, and the Fine and Gray competing risks regression was used to assess the prognostic association between these factors and time to PSA failure.ResultsThe study included 350 males who primarily had a good performance status (330 [94.3%] with Eastern Cooperative Oncology Group score of 0), median (range) age of 66 (43-86) years, with 167 (46.6%) having Gleason scores of 8 to 10, and 195 (55.2%) presenting with a baseline PSA of more than 10 ng/mL. After a median (IQR) follow-up of 10.2 (8.0-11.4) years, having a PSA level of 10 ng/mL to 20 ng/mL (subdistribution hazard ratio [sHR], 1.98; 95% CI, 1.28-3.07; P = .002) and a Gleason score of 8 to 10 (sHR, 2.55; 95% CI, 1.63-3.99; P &lt; .001) were associated with a shorter time to PSA failure, and older age (sHR, 0.82; 95% CI, 0.72-0.93; P = .002) was associated with reduced risk for PSA failure after adjusting for other baseline clinical factors. The high-risk category, defined by these 3 factors, was associated with a shorter time to PSA failure (sHR, 2.69; 95% CI, 1.84-3.93; P &lt; .001).Conclusions and RelevanceIn this secondary analysis of a randomized clinical trial of males with unfavorable risk PC, young age, PSA of 10 ng/mL or more, and a Gleason score of 8 to 10 estimated a shorter time to PSA failure. A subgroup of males at very high-risk for early PSA failure, as defined by our study, may benefit from treatment escalation with androgen receptor signaling inhibitors or cytotoxic chemotherapy and should be the subject of a prospective randomized clinical trial.Trial RegistrationNCT00116142

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Section: Discussionmentioning

confidence: 99%

Risk of Short-Term Prostate-Specific Antigen Recurrence and Failure in Patients With Prostate Cancer

Sayan,

Huang,

Xie

et al. 2023

JAMA Netw Open

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“…Beyond clinical and pathological measures, the GPS offers independent predictive information. Using biopsy tumor volumes from very small biopsy specimens, GPS assesses underlying biology to determine disease aggressiveness with greater accuracy, considering tumor heterogeneity and undersampling [34]. The Decipher test evaluates 22 cancer-related genes.…”

Section: Prognostic Biomarkers and Their Limitations In Prostate Cancermentioning

confidence: 99%

Aquaporins as Prognostic Biomarker in Prostate Cancer

Kushwaha

Verma

Gupta

2023

Cancers

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Prostate cancer is a complex heterogeneous disease that affects millions of males worldwide. Despite rapid advances in molecular biology and innovation in technology, few biomarkers have been forthcoming in prostate cancer. The currently available biomarkers for the prognosis of prostate cancer are inadequate and face challenges, thus having limited clinical utility. To date, there are a number of prognostic and predictive biomarkers identified for prostate cancer but lack specificity and sensitivity to guide clinical decision making. There is still tremendous scope for specific biomarkers to understand the natural history and complex biology of this heterogeneous disease, and to identify early treatment responses. Accumulative studies indicate that aquaporins (AQPs) a family of membrane water channels may serve as a prognostic biomarker for prostate cancer in monitoring disease advancement. In the present review, we discuss the existing prostate cancer biomarkers, their limitations, and aquaporins as a prospective biomarker of prognostic significance in prostate cancer.

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“…Currently used pathologic prognostic indicators do not adequately predict prostate cancer behavior in men with clinically localized disease [ 1 ]. To target men with appropriate, individualized treatment strategies or surveillance, new molecular markers that improve prognostic accuracy beyond the currently used pathologic stage, and Gleason sum (or grade group) are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy

Heaphy

Joshu

Barber

et al. 2022

The Journal of Pathology CR

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Current biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision‐making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer‐associated stromal cells – the telomere biomarker – is strongly associated with progression to metastasis and prostate cancer death after prostatectomy independent of currently used pathologic indicators. Here, we optimized our method allowing for semi‐automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in five cohort studies of men surgically treated for clinically localized disease ( N = 2,255). We estimated the relative risk (RR) of progression to metastasis ( N = 311) and prostate cancer death ( N = 85) using models appropriate to each study's design adjusting for age, prostatectomy stage, and tumor grade, which then we meta‐analyzed using inverse variance weights. Compared with men who had less variable telomere length among prostate cancer cells and longer telomere length in prostate cancer‐associated stromal cells, men with the combination of more variable and shorter telomere length had 3.76 times the risk of prostate cancer death (95% confidence interval [CI] 1.37–10.3, p = 0.01) and had 2.23 times the risk of progression to metastasis (95% CI 0.99–5.02, p = 0.05). The telomere biomarker was associated with prostate cancer death in men with intermediate risk disease (grade groups 2/3: RR = 9.18, 95% CI 1.14–74.0, p = 0.037) and with PTEN protein intact tumors (RR = 6.74, 95% CI 1.46–37.6, p = 0.015). In summary, the telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically treated men.

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Tissue-Based Biomarkers for the Risk Stratification of Men With Clinically Localized Prostate Cancer

Cited by 25 publications

References 78 publications

Risk of Short-Term Prostate-Specific Antigen Recurrence and Failure in Patients With Prostate Cancer

Risk of Short-Term Prostate-Specific Antigen Recurrence and Failure in Patients With Prostate Cancer

Aquaporins as Prognostic Biomarker in Prostate Cancer

The prostate tissue‐based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy

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